Effect of neoadjuvant chemoradiation on local control and disease-free survival in locally advanced rectal neoplasms

Year 2015, Volume: 4 Issue: 4, 338 - 350, 01.11.2015

Remzi Kurt Ertuğrul Karğı Çağrı Tiryaki Zülfü Bayhan Hakan Uzunoğlu Oğuz Özbay

https://doi.org/10.5505/abantmedj.2015.00377

Abstract

OBJECTIVE: Although surgery comprises the basis for the treatment of locally advanced rectal cancer, the feasibility of curative resection and sphincter-sparing surgery depending on the reduction in tumour size has been reported to increase with neoadjuvant chemoradiation CRT in patients with locally advanced rectal cancer. The aim of this study was to investigate recurrence, survival with disease/disease-free survival and factors affecting them in patients who underwent surgery after receiving neoadjuvant CRT.METHODS: The files of 79 patients aged older than 18 years who were diagnosed with locally advanced rectal cancer and underwent surgery after receiving neoadjuvant CRT between January 2007 and May 2012 were retrospectively analysed in terms of demographics and clinical, radiological and pathological data.RESULTS: : A total of 79 patients, among whom 27 34.2% were females and 52 65.8% were males, were included in the study, and the mean age was 60.82±5 years. The complete regression rate after neoadjuvant CRT was 15.18%. The average follow-up period of the patients was 26 months range: 3–59 months . During the follow up, tumour recurrence was detected in 28 35.44% patients, among whom 12 had local recurrence and 17 had systemic recurrence; the survival rate of the patients was 83.54%. The disease-free survival rate was 72.15%. In most of the patients, stage regression and the reduction of tumour size were achieved.CONCLUSION: In summary, hyperfractionated radiotherapy sterilises the margins of the mesorectum and prevents the development of tumour cell remnants, thus reducing the likelihood of local recurrence and preventing tumour cells from metastasising to remote organs. The ideal surgical technique after neoadjuvant CRT is total mesorectal excision. The important question is the optimum time for surgery after CRT. Thus, further studies are required to understand the long-term follow-up results of recurrence and survival/disease-free survival in patients with locally advanced rectal cancer who received long-term neoadjuvant CRT.

Keywords

Locally advanced rectal neoplasms, neoadjuvant chemoradiation, disease-free survival

Lokal İleri Evre Rektum Tümörlerinde Neoadjuvan Kemoradyoterapinin Lokal Kontrol ve Hastalıksız Sağkalım Üzerine Etkisi

Abstract

AMAÇ: Lokal ileri rektum kanserlerinde tedavinin temelini cerrahi oluştuşturmakla beraber neoadjuvan kemoradyoterapi KRT ile lokal ileri rektum kanserlerinde tümör boyutunda küçülmeye bağlı küratif rezeksiyon ve sfinkter koruyucu cerrahi yapılabilirliğinin arttığı bildirilmiştir. Bu çalışmanın amacı, neoadjuvan KRT aldıktan sonra cerrahi tedavi yapılan hastalarda rekürrens, hastalıksız /hastalıklı sağkalım ve buna etki eden faktörlerin araştırılmasıdır.YÖNTEMLER: Ocak 2007- Mayıs 2012 tarihleri arasında lokal ileri rektum kanseri tanısı konularak neoadjuvan KRT sonrası ameliyat edilmiş olan 18 yaş üstü 79 hastanın dosya kayıtları; demografik, klinik, radyolojik ve patolojik veriler açısından retrospektif olarak incelendi.BULGULAR: Çalışmaya 27 %34.2 kadın, 52 %65,8 erkek olmak üzere toplam 79 hasta katılmış olup ortalama yaş 60,82±5’ dir. Neoadjuvan KRT sonrası tam regresyon oranı %15,18’dir. Hastaların ortalama takip süresi, 26 ay 3-59 ay aralığında olarak saptandı. Takip süresince 28 %35,44 hastada tümör rekürrensi saptanmış olup bunun 12 tanesi lokal, 17 tanesi sistemik rekürrensti. Takip süresince hastaların hayatta kalımı %.83,54 idi. Hastalıksız sağ kalım ise %.72,15 idi. Hastaların büyük çoğunluğunda evre gerilemesi ve tümör boyutlarında küçülme sağlandı.SONUÇ: Hiperfraksiyone RT mezorektumun sınırlarını sterilize eder ve tümör hücre kalıntılarının gelişmesini engeller. Bu durum lokal nüks ihtimalini azaltır ve muhtemelen tümör hücrelerinin uzak organlara giderek metastaz yapmasını da engellemiş olur. Neoadjuvan KRT sonrası yapılacak ideal ameliyat tekniği Total mezorektal eksizyon‘ dur. Cevaplanması gereken önemli soru ise KRT sonrası ideal ameliyat zamanlamasının ne olduğudurÇalışmamızda olgu sayısının az olması ve takip süresinin kısa olması nedeni ile uzun dönem neoadjuvan kemoradyoterapi uygulanan lokal ileri rektum kanserli hastalarda nüks, sağkalım/ hastalıksız sağkalımın uzun dönem takip sonuçlarının anlaşılması için başka çalışmalara ihtiyaç vardır.

Keywords

Lokal ileri rektum kanseri, neadjuan kemoradyoterapi, hastalıksiz sağkalım

References

• Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007 Mar;18(3):581-592.
• Kulu Y, Muller-Stich BP, Bruckner T, Gehrig T, Buchler MW, Bergmann F, et al. Radical Surgery with Total Mesorectal Excision in Patients with T1 Rectal Cancer. Ann Surg Oncol. 2014 Oct 21.
• Shaikh I, Aston W, Hellawell G, Ross D, Littler S, Burling D, et al. Extended lateral pelvic sidewall excision (ELSiE): an approach to optimize complete resection rates in locally advanced or recurrent anorectal cancer involving the pelvic sidewall. Tech Coloproctol. 2014 Nov 8.
• Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005 May;241(5):829-836; discussion 836-828.
• Altini C, Niccoli Asabella A, De Luca R, Fanelli M, Caliandro C, Quartuccio N, et al. Comparison of F- FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer. Abdom Imaging. 2014 Oct 28.
• Agarwal A, Chang GJ, Hu CY, Taggart M, Rashid A, Park IJ, et al. Quantified pathologic response assessed as residual tumor burden is a predictor of recurrence-free survival in patients with rectal cancer who undergo resection after neoadjuvant chemoradiotherapy. 15;119(24):4231-4241.
• Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19-23.
• Ballinger AB, Anggiansah C. Colorectal cancer. Bmj. 2007 Oct 6;335(7622):715-718.
• Kehoe J, Khatri VP. Staging and prognosis of colon cancer. Surg Oncol Clin N Am. 2006 Jan;15(1):129-146.
• Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007 May 1;109(9):1750-1755.
• Eche N, Pichon MF, Quillien V, Gory-Delabaere G, Riedinger JM, Basuyau JP, et al. [Standards, options and recommendations for tumor markers in colorectal Dec;88(12):1177-1206.
• Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys. 1999 Jul 15;44(5):1027- 1038.
• Willett CG, Warland G, Coen J, Shellito PC, Compton CC. Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation. Int J Radiat Oncol Biol Phys. 1995 Apr 30;32(1):57-61.
• Bujko K, Michalski W, Kepka L, Nowacki MP, Nasierowska-Guttmejer A, Tokar P, et al. Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: An analysis of outcomes in a randomized trial. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):369-377.
• Lim SB, Yu CS, Hong YS, Kim TW, Kim JH, Kim JC. Long-term outcomes in patients with locally advanced rectal cancer treated with preoperative chemoradiation followed by curative surgical resection. J Surg Oncol. 2012 Nov;106(6):659-666.
• Luna-Perez P, Bustos-Cholico E, Alvarado I, Maffuz A, Rodriguez-Ramirez S, Gutierrez de la Barrera M, et al. Prognostic significance of circumferential margin involvement in rectal adenocarcinoma treated with preoperative chemoradiotherapy and low anterior resection. J Surg Oncol. 2005 Apr 1;90(1):20-25.
• Nagtegaal ID, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol. 2008 Jan 10;26(2):303- 312.
• Moriya Y, Hojo K, Sawada T, Koyama Y. Significance of lateral node dissection for advanced rectal carcinoma at or below the peritoneal reflection. Dis Colon Rectum. 1989 Apr;32(4):307- 315.
• Mohiuddin M, Regine WF, John WJ, Hagihara PF, McGrath PC, Kenady DE, et al. Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys. 2000 Mar 1;46(4):883-888.
• Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol. 1999 Aug;17(8):2396.
• Moore HG, Gittleman AE, Minsky BD, Wong D, Paty PB, Weiser M, et al. Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum. 2004 Mar;47(3):279-286.
• Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-1740.
• Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised 7;373(9666):811-820.
• Vogel C, Kirtil T, Oellig F, Stolte M. Lymph node preparation in resected colorectal carcinoma specimens employing the acetone clearing method. Pathol Res Pract. 2008;204(1):11-15.
• Fielding LP, Arsenault PA, Chapuis PH, Dent O, Gathright B, Hardcastle JD, et al. Clinicopathological staging for colorectal cancer: an International Documentation System (IDS) and an International Comprehensive Anatomical Terminology (ICAT). J Gastroenterol Hepatol. 1991 Jul-Aug;6(4):325-344.
• Krasna MJ, Flancbaum L, Cody RP, Shneibaum S, Ben Ari G. Vascular and neural invasion in colorectal carcinoma. Incidence and prognostic significance. Cancer. 1988 Mar 1;61(5):1018-1023.
• Talbot IC, Ritchie S, Leighton M, Hughes AO, Bussey HJ, Morson BC. Invasion of veins by carcinoma of rectum: method of detection, histological Histopathology. 1981 Mar;5(2):141-163. 28.
• Improvedradiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med. 1997 Apr 3;336(14):980-987.
• Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007 Nov;246(5):693-701.
• Pach R, Kulig J, Richter P, Gach T, Szura M, Kowalska T. Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer-- treatment results at 5-year follow-up. Langenbecks Arch Surg. 2012 Jun;397(5):801-807.
• Stipa F, Chessin DB, Shia J, Paty PB, Weiser M, Temple LK, et al. A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography. Aug;13(8):1047-1053.
• Wolthuis AM, Penninckx F, Haustermans K, De Hertogh G, Fieuws S, Van Cutsem E, et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol. 2012 Sep;19(9):2833-2841.